Plasmacytoid dendritic cells in allergic asthma and the role of inhaled corticosteroid treatment
Plasmacytoid dendritic cells in allergic asthma and the role of inhaled corticosteroid treatment
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DOI：
10.1111/cea.12064
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发表时间：
2013-03-01
影响因子：
6.1
通讯作者：
Virchow, J. C.
中科院分区：
文献类型：
--
作者：
Bratke, K.;Prieschenk, C.;Virchow, J. C.
背景：浆细胞样树突状细胞(PDCs)渗入急性Th2占优势的炎症部位，但其在过敏性哮喘中的作用尚不清楚。目的了解过敏性哮喘患者变应原季节外循环pDC的特征。方法采用流式细胞术对20例过敏性哮喘患者和18例健康对照外周血中的黏附分子、共刺激分子、免疫球蛋白受体和趋化因子受体进行定量检测。此外，用TLR7和TLR9配体刺激分离的PDDC，分析其分泌IL-6、肿瘤坏死因子和干扰素的情况。结果过敏性哮喘患者血浆细胞样树突状细胞表达与炎症组织归巢有关的趋化因子受体CCR2、CCR4、CCR9、CCR10、CXCR2、CXCR5和CXCR6，而淋巴归巢受体CXCR3表达下调。此外，CD40、CD62L、CD64和Fc epsilon RI等活化标志和Th2相关分子在PDCs中也有较高的表达。相反，哮喘患者pDC由TLR7介导的IL-6、TNF-和干扰素-α的分泌显著减少。TLR9介导的细胞因子反应仅在以前的过敏原季节接受吸入皮质类固醇(ICS)治疗的患者中受到抑制。CD54和OX40L的表达也有同样的影响。结论我们报道了过敏性哮喘患者活化标志物和Th2相关分子的表达增加，循环pDC的迁移能力增加。伴随这些变化的是TLR7介导的细胞因子反应减少。此外，我们的结果提示ICS治疗对循环pDC的特性有长期影响。
Background Plasmacytoid dendritic cells (pDCs) infiltrate sites of acute Th2-dominant inflammation, but their role in allergic asthma remains unclear. Objective To characterize circulating pDCs from patients with allergic asthma outside their respective allergen season. Methods Adhesion molecules, co-stimulatory molecules, immunoglobulin receptors and chemokine receptors were quantified on blood pDCs from 20 patients with allergic asthma and 18 healthy controls using flow cytometry. In addition, IL-6-, TNF-- and IFN--secretion were analysed after stimulating isolated pDCs with TLR7- and TLR9-ligands. Results Plasmacytoid dendritic cells from patients with allergic asthma showed an increased expression of chemokine receptors involved in inflamed tissue homing such as CCR2, CCR4, CCR9, CCR10, CXCR2, CXCR5 and CXCR6, while the expression of the lymph node homing receptor CXCR3 was down-regulated. In addition, these pDCs exhibited a higher expression of activation markers and Th2-associated molecules such as CD40, CD62L, CD64 and Fc epsilon RI. In contrast, TLR7-mediated IL-6-, TNF-- and IFN--secretion was significantly reduced in pDCs from patients with asthma. The TLR9-mediated cytokine response was only suppressed in those patients who were treated with inhaled corticosteroids (ICS) during previous allergen seasons. The same effect was observed for CD54 and OX40L expression. Conclusions We report an increased expression of activation markers, and Th2-associated molecules, and an increased migratory potential of circulating pDCs in allergic asthma. These changes are accompanied by a reduced TLR7-mediated cytokine response. In addition, our results suggest a longterm impact of ICS treatment on the characteristics of circulating pDCs.